Skip to main content

Do cognition and other non-motor symptoms decline similarly among patients with Parkinson’s disease motor subtypes? Findings from a 5-year prospective study

Journal of Neurology volume 264, pages 2149–2157 (2017)Cite this article

Abstract

Among patients with Parkinson’s disease (PD), a wide range of motor and non-motor symptoms (NMS) are evident. PD is often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD) motor subtypes. We evaluated the effect of disease duration and aimed to characterize whether there are differences in the deterioration of cognitive function and other NMS between the PIGD and TD subtypes. Sixty-three subjects were re-evaluated at the follow-up visit about 5 years after baseline examination. Cognitive function and other NMS were assessed. At follow-up, the PIGD and TD groups were similar with respect to medications, comorbidities and disease-related symptoms. There was a significant time effect for all measures, indicating deterioration and worsening in both groups. However, cognitive scores, particularly those related to executive function, became significantly worse in the PIGD with a more moderate decrease in the TD group. For example, the computerized global cognitive score declined in the PIGD group from 94.21 ± 11.88 to 83.91 ± 13.76, p < 0.001. This decline was significantly larger (p = 0.03) than the decrease observed in the TD group (96.56 ± 10.29 to 92.21 ± 14.20, p = 0.047). A significant group × time interaction effect was found for the change in global cognitive score (p = 0.047), the executive function index (p = 0.002) and accuracy on a motor-cognitive catch game (p = 0.008). In contrast, several NMS including depression, health-related quality of life and fear of falling deteriorated in parallel in both subtypes, with no interaction effect. The present findings highlight the difference in the natural history of the disease between the two PD “motor” subtypes. While the PIGD group demonstrated a significant cognitive decline, especially in executive functions, a more favorable course was observed in the TD subtype. This behavior was not seen in regards to the other NMS.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price includes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79:368–376

    CAS  Article  PubMed  Google Scholar 

  2. Chaudhuri KR, Odin P, Antonini A, Martinez-Martin P (2011) Parkinson’s disease: the non-motor issues. Parkinsonism Relat Disord 17:717–723

    Article  PubMed  Google Scholar 

  3. Duncan GW, Khoo TK, Yarnall AJ, O’Brien JT, Coleman SY, Brooks DJ, Barker RA, Burn DJ (2014) Health-related quality of life in early Parkinson’s disease: the impact of nonmotor symptoms. Mov Disord 29:195–202

    Article  PubMed  Google Scholar 

  4. Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, Chaudhuri KR (2011) The impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov Disord 26:399–406

    Article  PubMed  Google Scholar 

  5. Swick TJ, Friedman JH, Chaudhuri KR, Surmann E, Boroojerdi B, Moran K, Ghys L, Trenkwalder C (2014) Associations between severity of motor function and nonmotor symptoms in Parkinson’s disease: a post hoc analysis of the RECOVER Study. Eur Neurol 71:140–147

    Article  PubMed  Google Scholar 

  6. Ray CK, Rojo JM, Schapira AH, Brooks DJ, Stocchi F, Odin P, Antonini A, Brown RJ, Martinez-Martin P (2013) A proposal for a comprehensive grading of Parkinson’s disease severity combining motor and non-motor assessments: meeting an unmet need. PLoS One 8:e57221

    Article  Google Scholar 

  7. Zis P, Martinez-Martin P, Sauerbier A, Rizos A, Sharma JC, Worth PF, Sophia R, Silverdale M, Chaudhuri KR (2015) Non-motor symptoms burden in treated and untreated early Parkinson’s disease patients: argument for non-motor subtypes. Eur J Neurol 22:1145–1150

    CAS  Article  PubMed  Google Scholar 

  8. Dubois B, Pillon B (1997) Cognitive deficits in Parkinson’s disease. J Neurol 244:2–8

    CAS  Article  PubMed  Google Scholar 

  9. Herman T, Weiss A, Brozgol M, Wilf-Yarkoni A, Giladi N, Hausdorff JM (2015) Cognitive function and other non-motor features in non-demented Parkinson’s disease motor subtypes. J Neural Transm 122:1115–1124

    Article  PubMed  Google Scholar 

  10. Linder J, Birgander R, Olsson I, Riklund K, Larsson AK, Edstrom M, Stenlund H, Forsgren L (2009) Degenerative changes were common in brain magnetic resonance imaging in patients with newly diagnosed Parkinson’s disease in a population-based cohort. J Neurol 256:1671–1680

    Article  PubMed  Google Scholar 

  11. Muslimovic D, Post B, Speelman JD, Schmand B (2005) Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology 65:1239–1245

    Article  PubMed  Google Scholar 

  12. Verbaan D, Marinus J, Visser M, van Rooden SM, Stiggelbout AM, Middelkoop HA, van Hilten JJ (2007) Cognitive impairment in Parkinson’s disease. J Neurol Neurosurg Psychiatry 78:1182–1187

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Dirnberger G, Jahanshahi M (2013) Executive dysfunction in Parkinson’s disease: a review. J Neuropsychol 7:193–224

    Article  PubMed  Google Scholar 

  14. Kudlicka A, Clare L, Hindle JV (2011) Executive functions in Parkinson’s disease: systematic review and meta-analysis. Mov Disord 26:2305–2315

    Article  PubMed  Google Scholar 

  15. Taylor JP, Rowan EN, Lett D, O’Brien JT, McKeith IG, Burn DJ (2008) Poor attentional function predicts cognitive decline in patients with non-demented Parkinson’s disease independent of motor phenotype. J Neurol Neurosurg Psychiatry 79:1318–1323

    Article  PubMed  Google Scholar 

  16. Hoops S, Nazem S, Siderowf AD, Duda JE, Xie SX, Stern MB, Weintraub D (2009) Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology 73:1738–1745

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Jankovic J, McDermott M, Carter J, Gauthier S, Goetz C, Golbe L, Huber S, Koller W, Olanow C, Shoulson I (1990) Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology 40:1529–1534

    CAS  Article  PubMed  Google Scholar 

  18. Fahn S, Elton R, Members of the UPDRS development committee (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne D, Goldstein M (eds) Recent developments in Parkinson’s disease. Macmillan Health Care Information, Florham Park, pp 153–163

    Google Scholar 

  19. Selikhova M, Kempster PA, Revesz T, Holton JL, Lees AJ (2013) Neuropathological findings in benign tremulous parkinsonism. Mov Disord 28:145–152

    Article  PubMed  Google Scholar 

  20. Stebbins GT, Goetz CG, Burn DJ, Jankovic J, Khoo TK, Tilley BC (2013) How to identify tremor dominant and postural instability/gait difficulty groups with the movement disorder society unified Parkinson’s disease rating scale: comparison with the unified Parkinson’s disease rating scale. Mov Disord 28:668–670

    Article  PubMed  Google Scholar 

  21. Allcock LM, Kenny RA, Burn DJ (2006) Clinical phenotype of subjects with Parkinson’s disease and orthostatic hypotension: autonomic symptom and demographic comparison. Mov Disord 21:1851–1855

    Article  PubMed  Google Scholar 

  22. Ba F, Obaid M, Wieler M, Camicioli R, Martin WR (2016) Parkinson disease: the relationship between non-motor symptoms and motor phenotype. Can J Neurol Sci 43:261–267

    Article  PubMed  Google Scholar 

  23. Burn DJ, Landau S, Hindle JV, Samuel M, Wilson KC, Hurt CS, Brown RG (2012) Parkinson’s disease motor subtypes and mood. Mov Disord 27:379–386

    Article  PubMed  Google Scholar 

  24. Reijnders JS, Ehrt U, Lousberg R, Aarsland D, Leentjens AF (2009) The association between motor subtypes and psychopathology in Parkinson’s disease. Parkinsonism Relat Disord 15:379–382

    CAS  Article  PubMed  Google Scholar 

  25. Tremblay C, Achim AM, Macoir J, Monetta L (2013) The heterogeneity of cognitive symptoms in Parkinson’s disease: a meta-analysis. J Neurol Neurosurg Psychiatry 84:1265–1272

    Article  PubMed  Google Scholar 

  26. van der Hoek TC, Bus BA, Matui P, van der Marck MA, Esselink RA, Tendolkar I (2011) Prevalence of depression in Parkinson’s disease: effects of disease stage, motor subtype and gender. J Neurol Sci 310:220–224

    Article  PubMed  Google Scholar 

  27. Khoo TK, Yarnall AJ, Duncan GW, Coleman S, O’Brien JT, Brooks DJ, Barker RA, Burn DJ (2013) The spectrum of nonmotor symptoms in early Parkinson disease. Neurology 80:276–281

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wu Y, Guo XY, Wei QQ, Ou RW, Song W, Cao B, Zhao B, Shang HF (2016) Non-motor symptoms and quality of life in tremor dominant vs postural instability gait disorder Parkinson’s disease patients. Acta Neurol Scand 133:330–337

    CAS  Article  PubMed  Google Scholar 

  29. Rajput AH, Voll A, Rajput ML, Robinson CA, Rajput A (2009) Course in Parkinson disease subtypes: a 39-year clinicopathologic study. Neurology 73:206–212

    CAS  Article  PubMed  Google Scholar 

  30. Burn DJ, Rowan EN, Allan LM, Molloy S, O’Brien JT, McKeith IG (2006) Motor subtype and cognitive decline in Parkinson’s disease, Parkinson’s disease with dementia, and dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 77:585–589

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. Domellof ME, Elgh E, Forsgren L (2011) The relation between cognition and motor dysfunction in drug-naive newly diagnosed patients with Parkinson’s disease. Mov Disord 26:2183–2189

    Article  PubMed  Google Scholar 

  32. Lyros E, Messinis L, Papathanasopoulos P (2008) Does motor subtype influence neurocognitive performance in Parkinson’s disease without dementia? Eur J Neurol 15:262–267

    CAS  Article  PubMed  Google Scholar 

  33. Herman T, Weiss A, Brozgol M, Giladi N, Hausdorff JM (2014) Gait and balance in Parkinson’s disease subtypes: objective measures and classification considerations. J Neurol 261:2401–2410

    Article  PubMed  Google Scholar 

  34. Rosenberg-Katz K, Herman T, Jacob Y, Giladi N, Hendler T, Hausdorff JM (2013) Gray matter atrophy distinguishes between Parkinson disease motor subtypes. Neurology 80:1476–1484

    Article  PubMed  PubMed Central  Google Scholar 

  35. Goetz CG, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stebbins GT, Stern MB, Tilley BC, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, Van Hilten JJ, LaPelle N (2007) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): process, format, and clinimetric testing plan. Mov Disord 22:41–47

    Article  PubMed  Google Scholar 

  36. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N (2008) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23:2129–2170

    Article  PubMed  Google Scholar 

  37. Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE (2010) Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord 25:2649–2653

    Article  PubMed  Google Scholar 

  38. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    CAS  Article  PubMed  Google Scholar 

  39. Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53:695–699

    Article  PubMed  Google Scholar 

  40. Doniger GM, Simon ES, Schweiger A (2008) Adjustment of cognitive scores with a co-normed estimate of premorbid intelligence: implementation using mindstreams computerized testing. Appl Neuropsychol 15:250–263

    Article  PubMed  Google Scholar 

  41. Hausdorff JM, Doniger GM, Springer S, Yogev G, Giladi N, Simon ES (2006) A common cognitive profile in elderly fallers and in patients with Parkinson’s disease: the prominence of impaired executive function and attention. Exp Aging Res 32:411–429

    Article  PubMed  PubMed Central  Google Scholar 

  42. Powell LE, Myers AM (1995) The Activities-specific Balance Confidence (ABC) Scale. J Gerontol A Biol Sci Med Sci 50A:M28–M34

    CAS  Article  PubMed  Google Scholar 

  43. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO (1982) Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 17:37–49

    Article  PubMed  Google Scholar 

  44. Chaudhuri KR, Martinez-Martin P (2008) Quantitation of non-motor symptoms in Parkinson’s disease. Eur J Neurol 15(Suppl 2):2–7

    Article  PubMed  Google Scholar 

  45. Peto V, Jenkinson C, Fitzpatrick R, Greenhall R (1995) The development and validation of a short measure of functioning and well being for individuals with Parkinson’s disease. Qual Life Res 4:241–248

    CAS  Article  PubMed  Google Scholar 

  46. Alves G, Larsen JP, Emre M, Wentzel-Larsen T, Aarsland D (2006) Changes in motor subtype and risk for incident dementia in Parkinson’s disease. Mov Disord 21:1123–1130

    Article  PubMed  Google Scholar 

  47. Williams-Gray CH, Foltynie T, Brayne CE, Robbins TW, Barker RA (2007) Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain 130:1787–1798

    CAS  Article  PubMed  Google Scholar 

  48. Maidan I, Nieuwhof F, Bernad-Elazari H, Reelick MF, Bloem BR, Giladi N, Deutsch JE, Hausdorff JM, Claassen JA, Mirelman A (2016) The role of the frontal lobe in complex walking among patients with Parkinson’s disease and healthy older adults: an fNIRS study. Neurorehabil Neural Repair 30:963–971

    Article  PubMed  Google Scholar 

  49. Stuss DT, Levine B (2002) Adult clinical neuropsychology: lessons from studies of the frontal lobes. Annu Rev Psychol 53:401–433

    Article  PubMed  Google Scholar 

  50. Maidan I, Rosenberg-Katz K, Jacob Y, Giladi N, Deutsch JE, Hausdorff JM, Mirelman A (2016) Altered brain activation in complex walking conditions in patients with Parkinson’s disease. Parkinsonism Relat Disord 25:91–96

    CAS  Article  PubMed  Google Scholar 

  51. Factor SA, Steenland NK, Higgins DS, Molho ES, Kay DM, Montimurro J, Rosen AR, Zabetian CP, Payami H (2011) Postural instability/gait disturbance in Parkinson’s disease has distinct subtypes: an exploratory analysis. J Neurol Neurosurg Psychiatry 82:564–568

    Article  PubMed  Google Scholar 

  52. Selikhova M, Williams DR, Kempster PA, Holton JL, Revesz T, Lees AJ (2009) A clinico-pathological study of subtypes in Parkinson’s disease. Brain 132:2947–2957

    CAS  Article  PubMed  Google Scholar 

  53. Nutt JG (2016) Motor subtype in Parkinson’s disease: different disorders or different stages of disease? Mov Disord 31:957–961

    Article  PubMed  Google Scholar 

  54. Antonini A, Barone P, Marconi R, Morgante L, Zappulla S, Pontieri FE, Ramat S, Ceravolo MG, Meco G, Cicarelli G, Pederzoli M, Manfredi M, Ceravolo R, Mucchiut M, Volpe G, Abbruzzese G, Bottacchi E, Bartolomei L, Ciacci G, Cannas A, Randisi MG, Petrone A, Baratti M, Toni V, Cossu G, Del DP, Bentivoglio AR, Abrignani M, Scala R, Pennisi F, Quatrale R, Gaglio RM, Nicoletti A, Perini M, Avarello T, Pisani A, Scaglioni A, Martinelli PE, Iemolo F, Ferigo L, Simone P, Soliveri P, Troianiello B, Consoli D, Mauro A, Lopiano L, Nastasi G, Colosimo C (2012) The progression of non-motor symptoms in Parkinson’s disease and their contribution to motor disability and quality of life. J Neurol 259:2621–2631

    Article  PubMed  Google Scholar 

  55. Erro R, Picillo M, Vitale C, Amboni M, Moccia M, Santangelo G, Pellecchia MT, Barone P (2016) The non-motor side of the honeymoon period of Parkinson’s disease and its relationship with quality of life: a 4-year longitudinal study. Eur J Neurol 23:1673–1679

    CAS  Article  PubMed  Google Scholar 

  56. Muller B, Assmus J, Herlofson K, Larsen JP, Tysnes OB (2013) Importance of motor vs. non-motor symptoms for health-related quality of life in early Parkinson’s disease. Parkinsonism Relat Disord 19:1027–1032

    Article  PubMed  Google Scholar 

  57. Prakash KM, Nadkarni NV, Lye WK, Yong MH, Tan EK (2016) The impact of non-motor symptoms on the quality of life of Parkinson’s disease patients: a longitudinal study. Eur J Neurol 23:854–860

    CAS  Article  PubMed  Google Scholar 

  58. Zis P, Rizos A, Martinez-Martin P, Pal S, Silverdale M, Sharma JC, Sauerbier A, Chaudhuri KR (2014) Non-motor symptoms profile and burden in drug naive versus long-term Parkinson’s disease patients. J Parkinson’s Dis 4:541–547

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for the Study of Movement, Cognition and Mobility, Neurological Institute, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 64239, Tel Aviv, Israel

    L. Arie, Talia Herman, S. Shema-Shiratzky, N. Giladi & J. M. Hausdorff

  2. Department of Physical Therapy, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    L. Arie & J. M. Hausdorff

  3. Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel

    N. Giladi & J. M. Hausdorff

  4. Department of Neurology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    N. Giladi

  5. Rush Alzheimer’s Disease Center, Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, USA

    J. M. Hausdorff

Authors
  1. L. Arie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Talia Herman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Shema-Shiratzky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Giladi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. M. Hausdorff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Talia Herman.

Ethics declarations

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards

The study was conducted in compliance with the regulations of the local ethics committee and in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent to participate in the study was obtained from all participants.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Arie, L., Herman, T., Shema-Shiratzky, S. et al. Do cognition and other non-motor symptoms decline similarly among patients with Parkinson’s disease motor subtypes? Findings from a 5-year prospective study. J Neurol 264, 2149–2157 (2017). https://doi.org/10.1007/s00415-017-8605-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-017-8605-x

Keywords

  • Parkinson’s disease
  • Motor subtypes
  • Cognitive decline
  • Non-motor symptoms
  • Prospective
  • PIGD